Development of high-efficiency gene targeting technologies

• Project/Area Number: 15H04323
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: System genome science
• Research Institution: Yokohama City University
• Principal Investigator: Noritaka Adachi 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (30264675)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: ジーンターゲティング / ヒトゲノム / ゲノム編集 / DNA修復 / ゲノム修復

Outline of Final Research Achievements

In this research project, we have successfully identified a human protein that is essential for alternative end-joining, a minor pathway of DNA double-strand break repair. This discovery has led us to develop a unique system to suppress random integration of transfected DNA, making it possible to perform human cell gene targeting with 100% efficiency.

Research Products

• [Int'l Joint Research] 南カリフォルニア大学/MDアンダーソンがん研究所(米国)
• [Journal Article] Dual loss of human POLQ and LIG4 abolishes random integration. (2017)
  • Author(s): Saito S, Maeda R, Adachi N.
  • Journal Title: Nature Commun. Volume: 8 Issue: 1
  • DOI: 10.1038/ncomms16112
  • Peer Reviewed / Open Access
• [Journal Article] Mechanistic basis for increased human gene targeting by promoterless vectors: roles of homology arms and Rad54 paralogs. (2017)
  • Author(s): Saito S, Kurosawa A, Adachi N.
  • Journal Title: FEBS J. Volume: 284 Issue: 17 Pages: 2748-2763
  • DOI: 10.1111/febs.14137
  • Peer Reviewed / Open Access
• [Journal Article] Non-homologous DNA end joining and alternative pathways to double-strand break repair. (2017)
  • Author(s): Chang HHY, Pannunzio NR, Adachi N, Lieber MR.
  • Journal Title: Nature Rev. Mol. Cell Biol. Volume: 18 Issue: 8 Pages: 495-506
  • DOI: 10.1038/nrm.2017.48
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dual loss of human POLQ and LIG4 abolishes random integration (2017)
  • Author(s): Saito S, Maeda R, Adachi N.
  • Journal Title: Nat. Commun. Volume: in press
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TBP-like Protein (TLP) Disrupts the p53-MDM2 Interaction and Induces Long-lasting p53 Activation. (2017)
  • Author(s): Maeda R., Tamashira H., Takano K., Takahashi H., Suzuki H., Saito S., Hojima W., Adachi N., U ra K ., E ndo T . and *Tam ura T.
  • Journal Title: J. Biol. Chem. Volume: 292 Issue: 8 Pages: 3201-3212
  • DOI: 10.1074/jbc.m116.763318
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency. (2016)
  • Author(s): Saito S, Kurosawa A, Adachi N.
  • Journal Title: J Hum Genet. Volume: 印刷中 Issue: 8 Pages: 679-685
  • DOI: 10.1038/jhg.2016.46
  • NAID: 40020923702
  • Peer Reviewed
• [Journal Article] Advances in the Development of Gene-Targeting Vectors to Increase the Efficiency of Genetic Modification (2016)
  • Author(s): Saito S, Adachi N.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 39 Issue: 1 Pages: 25-32
  • DOI: 10.1248/bpb.b15-00701
  • NAID: 130005116505
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Construction and applications of exon-trapping gene-targeting vectors with a novel strategy for negative selection. (2015)
  • Author(s): Saito S, Ura K, Kodama M, Adachi N.
  • Journal Title: BMC Res Notes. Volume: 8 Issue: 1 Pages: 278-278
  • DOI: 10.1186/s13104-015-1241-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant